Project Summary The objective of this research proposal is to develop new asymmetric catalytic protocols for hydro- and di-functionalization of unactivated alkenes. Alkenes are some of the most simple chemical building blocks that can be readily elaborated to give products of high value. From our longstanding interest in reversing the typical reactivity patterns of alkenes, we have developed a catalyst system that affords the opposite, or anti-Markovnikov, regioisomers of alkene hydrofunctionalization products. In Specific Aim 1, we will develop a new catalyst system to accomplish these reactions with control of absolute stereochemistry. In Specific Aim 2, we will develop new difunctionalization reactions of alkenes based on this general catalyst system that provides the opposite regioselectivity for what is typically observed in previously established methods. In this aim we will also delineate conditions to accomplish these reactions with stereochemical control. We predict that this research program will enhance the synthetic capabilities of medicinal chemists to explore greater chemical space in the development of small molecule therapeutics.